Chemical engineering processes and apparatus for the synthesis of compounds
The present invention provides methods for producing cannabinoids and cannabinoid analogs as well as a system for producing these compounds. The inventive method is directed to contacting a compound according to Formula I or Formula II with a cannabinoid synthase. Also described is a system for producing cannabinoids and cannabinoid analogs by contacting a THCA synthase with a cannabinoid precursor and modifying at least one property of the reaction mixture to influence the quantity formed of a first cannabinoid relative to the quantity formed of a second cannabinoid.
1. A method of producing one or more cannabinoids comprising:
reacting a compound according to Formula I:
with a recombinant cannabinoid synthase as a catalyst in a reaction mixture;
controlling a property of the reaction mixture to modify the amount of the one or more cannabinoids which are catalyzed by the recombinant cannabinoid synthase;
wherein
R 1 is H or —COOH;
R 2 is selected from the group consisting of linear or branched CH 3 , C 2 H 5 , C 3 H 7 , C 4 H 9 , C 6 H 13 , C 7 H 15 and C 8 H 17 ; and
wherein the cannabinoid synthase is selected from the group consisting of a cannabidiolic acid synthase and a tetrahydrocannabinolic acid synthase;
wherein the reaction mixture comprises dimethyl sulfoxide (DMSO), and wherein the amount of the DMSO in the reaction mixture is between 5% and 30% (v/v).
2. The method of claim 1 , wherein R 2 is selected from the group consisting of linear CH 3 , C 2 H 5 , C 3 H 7 , C 4 H 9 , C 6 H 13 , C 7 H 15 and C 8 H 17 .
3. The method of claim 2 , wherein R 2 is a linear C 3 H 7 group.
4. The method of claim 1 , further comprising conjugating the recombinant cannabinoid synthase to a solid support.
5. The method of claim 1 , wherein the cannabinoid is a single enantiomer.
6. The method of claim 1 , wherein the enantiomeric purity of the cannabinoid is at least 95%.
7. The method of claim 6 , wherein the enantiomeric purity of the cannabinoid is at least 99%.
8. The method of claim 1 , wherein the recombinant cannabinoid synthase is a recombinant tetrahydrocannabinolic acid synthase (THCA synthase).
9. The method of claim 1 , wherein the recombinant cannabinoid synthase is overexpressed in a host cell.
10. The method of claim 9 , wherein the recombinant cannabinoid synthase is THCA synthase.
11. The method of claim 10 , wherein the THCA synthase is overexpressed in yeast or in Escherichia coli.
12. The method of claim 1 , wherein the recombinant cannabinoid synthase is cannabidiolic acid (CBDA) synthase.
13. The method of claim 1 , further comprising isolating the cannabinoid.
14. The method of claim 1 , further comprising decarboxylating the cannabinoid.
15. The method of claim 1 , wherein the property is pH of the reaction mixture.
16. The method of claim 15 , wherein the pH of the reaction mixture is between 4.0 and 8.0.